Cell-Derived N/P/S-Codoped Fluorescent Carbon Nanodots with Intrinsic Targeting Ability for Tumor-Specific Phototheranostics.

Combining targeting ability, imaging function, and photothermal/photodynamic therapy into a single agent is highly desired for cancer theranostics. Herein, we developed a one-for-all nanoplatform with N/P/S-codoped fluorescent carbon nanodots (CNDs) for tumor-specific phototheranostics. The CNDs were prepared via a one-pot hydrothermal process using cancer cells as sources of carbon, nitrogen, phosphorus, and sulfur. The obtained N/P/S-codoped CNDs exhibit wide light absorption in the range of 200-900 nm and excitation-dependent emission with high photostability. Importantly, the cancer cell-derived N/P/S-codoped CNDs have outstanding biocompatibility and naturally intrinsic targeted ability for cancer cells as well as dual photothermal/photodynamic effects under 795 nm laser irradiation. Moreover, the photothermal conversion efficiency and singlet oxygen (1O2) generation efficiency were calculated to be 52 and 34%, respectively. These exceptional properties enable CNDs to act as fine theranostic agents for targeted imaging and photothermal-photodynamic synergistic therapy within the NIR therapeutic window. The CNDs prepared in this work are promising for construction as a universal tumor phototheranostic platform.

Functional characterization and structural basis of a reversible glycosyltransferase involves in plant chemical defence.

Plants experience numerous biotic stresses throughout their lifespan, such as pathogens and pests, which can substantially affect crop production. In response, plants have evolved various metabolites that help them withstand these stresses. Here, we show that two specialized metabolites in the herbaceous perennial Belamcanda chinensis, tectorigenin and its glycoside tectoridin, have diverse defensive effects against phytopathogenic microorganisms and antifeeding effects against insect pest. We further functionally characterized a 7-O-uridine diphosphate glycosyltransferase Bc7OUGT, which catalyses a novel reversible glycosylation of tectorigenin and tectoridin. To elucidate the catalytic mechanisms of Bc7OUGT, we solved its crystal structure in complex with UDP and UDP/tectorigenin respectively. Structural analysis revealed the Bc7OUGT possesses a narrow but novel substrate-binding pocket made up by plentiful aromatic residues. Further structure-guided mutagenesis of these residues increased both glycosylation and deglycosylation activities. The catalytic reversibility of Bc7OUGT was also successfully applied in an one-pot aglycon exchange reaction. Our findings demonstrated the promising biopesticide activity of tectorigenin and its glycosides, and the characterization and mechanistic study of Bc7OUGT could facilitate the design of novel reversible UGTs to produce valuable glycosides with health benefits for both plants and humans.

Postoperative adjuvant immunotherapy for high-risk hepatocellular carcinoma patients.

Background and aim: Standardized approach to postoperative adjuvant therapy for hepatocellular carcinoma (HCC) remains elusive. This study endeavors to examine the effects of postoperative PD-1 adjuvant therapy on the short-term and long-term prognosis of patients at a heightened risk of post-surgical recurrence. Methods: The data of HCC patients who underwent hepatectomy at our center from June 2018 to March 2023 were collected from the hospital database. Propensity score matching (PSM) was employed to perform a 1:1 match between the postoperative anti-PD-1 antibody group and the postoperative non-anti-PD-1 antibody group. Kaplan-Meier method was utilized to compare the overall survival (OS) and recurrence-free survival (RFS) between the two groups. Cox regression analysis was conducted to identify the prognostic factors affecting patient outcomes. Subgroup analyses were performed for different high-risk factors. Results: Among the 446 patients included in the study, 122 patients received adjuvant therapy with postoperative anti-PD-1 antibodies. After PSM, the PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year OS rates of 93.1%, 86.8%, 78.2%, and 51.1%, respectively, while the non-PD-1 group had rates of 85.3%, 70.2%, 47.7%, and 30.0%. The PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year RFS rates of 81.7%, 77.0%, 52.3%, and 23.1%, respectively, whereas the non-PD-1 group had rates of 68.4%, 47.7%, and 25.8% in 1-year, 2-year, 3-year. A multifactorial Cox regression analysis revealed that postoperative PD-1 use was a prognostic protective factor associated with OS and RFS. Subgroup analysis results indicated that HCC patients with high recurrence risks significantly benefited from postoperative anti-PD-1 antibody treatment in terms of OS and RFS. Conclusion: For HCC patients with high-risk recurrence factors and undergoing hepatectomy, postoperative adjuvant therapy with anti-PD-1 antibodies can effectively improve their survival prognosis.

Chordin-Like 2: A Possible Therapeutic Target for Gastric Cancer by Affecting Cell Cycle and Proliferation.

Purpose: This study aimed to examine the role of chordin-like 2 (CHRDL2) in gastric cancer. Methods: The Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets were screened and the differentially expressed gene CHRDL2 was identified. The CHRDL2 expression was examined in the Human Protein Atlas and TCGA. Clinical data on gastric cancer were evaluated for their association with CHRDL2 by using TCGA and KM-plotter databases. The possible relationship amongst CHRDL2, immune cells, and related genes was investigated via the TIMER database. Enrichment analysis was performed using GO and KEGG pathways to explore the mechanisms. Results: Screening of databases revealed that CHRDL2 was a differentially expressed gene. An increase in cytoplasmic CHRDL2 expression was found in cancer tissues compared with the surrounding normal tissues. The data, together with those from TCGA and the KM-plotter databases, showed that patients with gastric cancer with high level of CHRDL2 have worse prognosis than those with low expression. A strong correlation was found between CHRDL2 expression and T stage, race, pathological grade, and pathological type according to clinical data analysis. CHRDL2 expression is linked to immune infiltration, as shown by the TIMER database. The data suggested that CHRDL2 plays a pivotal role in the tumor microenvironment of gastric cancer and might help tumor cells evade the immune system. Gene set enrichment analysis showed that CHRDL2 is involved in the chemokine signaling route, the intestinal immune network, the MAPK pathway, cell cycle, and the PI3K-Akt signaling system that are associated with the pathological processes of gastric cancer. Conclusion: Patients with gastric cancer with decreased CHRDL2 levels have dramatically improved OS, PFS, and PPS. CHRDL2 plays a pivotal role in enabling tumor cell immune evasion in tumor microenvironment, suggesting a function of this gene in the development of gastric cancer and its immune infiltration. Interfering with CHRDL2 may slow down the development of this malignancy by affecting cell cycle and apoptosis pathways.

The Role of Circulating Tumor Cells in the Prognosis of Local Recurrence and Local Residual Nasopharyngeal Carcinoma Undergoing Endoscopic Resection.

Purpose: To investigate the role of circulating tumor cells in the prognosis of local recurrence and local residual nasopharyngeal carcinoma undergoing endoscopic surgery. Methods: A total of 56 patients with locally residual nasopharyngeal carcinoma (NPC) who underwent nasal endoscopic surgery from August 2018 to December 2021 were included. The status of circulating tumor cells (CTC) before and after surgery was detected, and its relationship with clinical characteristics and postoperative survival was analyzed. Results: After nasal endoscopy, the positive rates of CTC and mesenchymal CTC (MCTC) detected in patients with nasopharyngeal carcinoma were significantly lower than those before treatment (P=0.0376; P=0.0212). Before nasal endoscopy, the status of CTC and MCTC was significantly correlated with the T stage (P < 0.05). After nasal endoscopy, the status of CTC and MCTC was significantly correlated with the TNM stage, T stage, and first radiotherapy mode (P < 0.05). The PFS of patients with different clinical characteristics was analyzed, and the results showed that the PFS of NPC patients with CTC (+) was significantly shorter than that of CTC (-) patients (18.71 vs. 22.47, P < 0.05) and the PFS of NPC patients with MCTC (+) was significantly shorter than that of MCTC (-) patients (18.22 vs. 22.30, P < 0.05). The PFS of NPC patients in TNM stage (I-II) was significantly longer than that in TNM stage (III) patients (22.53 vs. 18.57, P < 0.05). The PFS of NPC patients whose first radiotherapy mode was conventional was significantly longer than that of patients whose first radiotherapy mode was enhanced (22.14 vs. 16.85, P < 0.05). The COX analysis showed that MCTC and TNM stages were independent risk factors affecting the prognosis of local recurrence or local residual nasopharyngeal carcinoma after endoscopic resection (P < 0.05). Conclusion: The detection of CTC is helpful for the prognosis evaluation of local recurrence or local residual NPC after endoscopic resection of NPC. The MCTC is an important factor affecting the prognosis of NPC patients.

Circulating Tumor Cells as an Indicator of Treatment Options for Hepatocellular Carcinoma Less Than or Equal to 3†cm in Size: A Multi-Center, Retrospective Study.

Background: The status of circulating tumor cells (CTCs) is related to the recurrence of hepatocellular carcinoma (HCC), which is also one of the reasons for the poor prognosis of HCC. The purpose of this study was to explore whether CTCs can help guide the choice of treatment methods for HCC. Methods: This study is a multicenter retrospective study, including 602 patients with HCC. CTCs were detected in the overall cohort before operation. There were 361 patients in the training cohort and 241 patients in the validation cohort. Patients were divided into CTC-negative group (CTCs = 0/5 mL) and the CTC-positive group (CTCs ≥ 1/5 mL) according to CTCs status. Subgroup analysis was performed according to CTCs status. We compared overall survival, and recurrence outcomes for HCC patients with different CTC statuses after undergoing radiofrequency ablation (RFA) or surgical resection (SR). Results: There was no significant difference in overall survival (OS) and recurrence-free survival (RFS) between the RFA group and SR group for CTC-negative patients in both the training cohort and the validation cohort (P > 0.05). However, among CTC-positive patients, the clinical outcome of patients in the SR group was significantly better than those in the RFA group. CTC-positive patients who underwent RFA had increased early recurrence compared to those who underwent SR. RFA is an independent risk factor for survival and recurrence in CTC-positive HCC patients. Conclusions: The CTC status could serve as an indicator to guide the choice between surgical resection or radiofrequency ablation for early hepatocellular carcinoma. Surgical resection is recommended for CTC-positive patients.

Oroxylin a could be a Promising Radiosensitizer for Esophageal Squamous Cell Carcinoma by Inducing G2/M Arrest and Activating Apoptosis.

To evaluate the radiosensitization of Oroxylin A on esophageal carcinoma cell as well as the optimal scheduling of Oroxylin A and radiotherapy (RT). Cell proliferation was estimated by a CCK8 assay. Radiosensitization was evaluated by a clonogenic survival assay. The progressions of Cell apoptosis and Cell cycle were investigated by flow cytometry. Expressions of survivin and cell cycle regulators were evaluated by Western blot analysis. A dose-dependent cell survival reduction was found in response to radiation with or without Oroxylin A. The apoptosis rates were remarkably dose-dependent higher in combination groups than in either Oroxylin A or radiation alone group. Besides, Oroxylin A could obviously radiosensitize ESCC cells by arresting tumor cells in G2/M phase and regulating cyclin B1 and Cdc 2 protein expression. Oroxylin A could be a promising radiosensitizer for esophageal squamous cell carcinoma by inducing G2/M phase blocking and activating cell apoptosis.

LncRNAs and their role in cancer stem cells.

Cancer stem cells (CSCs) play a vital role in the formation of tumors and have been studied as a target of anticancer therapy. Long non-coding RNAs (lncRNAs) are important in the genesis and progression of cancer. Various lncRNAs, such as ROR, HOTAIR, H19, UCA1, and ARSR, are involved in cancer stemness. These lncRNAs could regulate the expression of CSC-related transcriptional factors, such as SOX2, OCT4, and NANOG, in colorectal, prostate, bladder, breast, liver, and other cancer types. In this work, we review the progress of lncRNAs and cancer stem cells and discuss the potential signal pathways of lncRNAs in cancer stemness.

Esophageal cancer stem cells and implications for future therapeutics.

Esophageal carcinoma (EC) is a lethal disease with high morbidity and mortality worldwide, and the incidence has been increasing in recent years. Although the diagnosis and treatment of EC have improved considerably, EC has rapidly progressed in the clinical setting and has a poor prognosis for its metastasis and recurrence. The general idea of cancer stem cells (CSCs) is primarily based on clinical and experimental observations, indicating the existence of a subpopulation of cells that can self-renew and differentiate. The EC stem cells, which can be isolated from normal pluripotent stem cells by applying similar biomarkers, may participate in promoting esophageal tumorigenesis through renewal and repair. In this review, major emphasis is given to CSC markers, altered CSC-specific pathways, and molecular targeting agents currently available to target CSCs of esophageal cancer. The roles of numerous markers (CD44, aldehyde dehydrogenase, CD133, and ATP-binding cassette subfamily G member 2) and developmental signaling pathways (Wnt/ß-catenin, Notch, hedgehog, and Hippo) in isolating esophageal CSCs are discussed in detail. Targeting CSCs can be a logical strategy to treat EC, as these cells are responsible for carcinoma recurrence and chemoradiation resistance.

Potential biomarkers for esophageal cancer.

Esophageal cancer, which consist of esophageal adenocarcinoma and esophageal squamous cell carcinoma, is one of the most common malignant tumors in the world, especially in the south of Iran and China. To find and investigate the biomarkers in the initiation, development and progression of esophageal cancer will help us predict the prognosis of esophageal cancer patients and improve the curative effect and survival rate. Here, we reviewed the potential biomarkers of esophageal cancer in three aspects: Immunohistochemical markers, blood-based markers, miRNA markers and Gene expression profiling. All these biomarkers provided promising therapeutic targets for the diagnosis, treatment, and prognosis of esophageal cancer.

Salinomycin radiosensitizes human nasopharyngeal carcinoma cell line CNE-2 to radiation.

Nasopharyngeal carcinoma (NPC) is primarily treated by chemoradiation. However, how to promote radiation sensitivity in NPC remains a challenge. Salinomycin is potentially useful for the treatment of cancer. This study aimed to explore the radiosensitivity of salinomycin on human nasopharyngeal carcinoma cell line CNE-2. CNE-2 were treated with salinomycin or irradiation, alone or in combination. The cytotoxicity effects of salinomycin were measured using CCK-8 assay. Clonogenic survival assay was used to evaluate the effects of salinomycin on the radiosensitivity of CNE-2. The changes of cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of Caspase3/Bax/Bal-2 was detected by Western blotting. DNA damage was detected via γ-H2AX foci counting. The results showed that salinomycin induced apoptosis and G2/M arrest, increased Bax and cleaved Caspase3, decreased Bcl-2 expression, and increased the formation of γ-H2AX nuclear foci. These data suggest that salinomycin may be a radiosensitizer for NPC radiotherapy.

The natural compound gambogic acid radiosensitizes nasopharyngeal carcinoma cells under hypoxic conditions.

AIMS: Hypoxia is an important factor that causes decreased local disease control as well as increased distant metastases and resistance to radiotherapy in patients with advanced nasopharyngeal carcinoma (NPC). Gambogic acid (GA), the major active ingredient of gamboge, exerts antitumor effects in vitro and in vivo. However, the molecular mechanism by which GA inhibits tumor radioresistance remains unclear. The present study aimed to investigate the radiosensitizing effects of GA on NPC and explore the underlying mechanisms. MATERIALS AND METHODS: CNE-1 and CNE-2 cells exposed to hypoxia and radiation were treated with GA at different concentrations. CCK-8 assay, clonogenic assay, and flow cytometry were performed to analyze cell proliferation, colony formation, apoptosis, and cell cycle. The expression levels of hypoxia-inducible factor-1α (HIF-1α), Bcl-2, Bax, caspase-3, cyclin B1/p-cdc2 and γ-H2AX were assessed using Western blot and/or immunofluorescence analysis. RESULTS: Results of the CCK-8 assay, clonogenic assay, and flow cytometry showed that treatment of NPC cells with growth-suppressive concentrations of GA resulted in G2/M phase arrest and apoptosis. Western blot analysis demonstrated that GA-induced cell cycle arrest and apoptosis in CNE-2 cells was associated with upregulated expression of caspase-3 and Bax and downregulated expression of Bcl-2 and cyclin B1/p-cdc2 in hypoxia. Treatment with GA markedly decreased the expression of HIF-1α under hypoxic conditions. CONCLUSIONS: The results of this study suggest that GA efficiently radiosensitizes NPC cells and the effect may be significant in hypoxic conditions.